Association of an inflammaging score based on IL-6, IL-10 and CXCL9, and frailty with long-term mortality in hospitalized older adults

Aging is accompanied by chronic low-grade inflammation ("inflammaging"), which contributes to increased morbidity and mortality in older adults. This study evaluated the prognostic value of circulating inflammatory biomarkers, i.e. interleukin-6 (IL-6), interleukin-10 (IL-10), and CXCL9, and their integration with frailty for long-term risk stratification. We analyzed 1,009 patients (median age, 84 years) hospitalized in acute care wards of three Italian geriatric hospitals as part of the ReportAGE cohort. Frailty was assessed using a deficit accumulation–based Frailty Index (FI), and serum cytokines were measured by immunoassay. Cytokine-specific risk categories were combined into a composite I3 score (range, 3–9). Cox proportional hazards models adjusted for age, sex, comorbidity burden, polypharmacy, and laboratory variables were used to assess associations with 10-year mortality. In a subset of 237 patients, DNA methylation–based estimates of cytokine levels were also analyzed. Higher I3 scores were independently associated with increased mortality (hazard ratio [HR] 2.42, 95% CI 1.74–3.37 for high vs. low scores), with CXCL9 as the strongest individual predictor (HR 1.69, 95% CI 1.30–2.19). The I3 score improved risk prediction beyond FI alone, and their combination identified four distinct risk groups, with the highest mortality observed among patients with both elevated FI and I3 scores. The integrated model (Clinical variables + FI + I3) achieved the greatest discrimination during the first seven years of follow-up. Serum IL-6 and CXCL9 correlated with their DNA methylation–based estimates, supporting an epigenetic contribution to chronic inflammation. The I3 score complements frailty assessment and enhances long-term mortality prediction in hospitalized older adults.

Authors

Institutions

Publication Details

Journal
Immunity & Ageing
Published
2025-12-19
DOI
https://doi.org/10.1186/s12979-025-00553-5
Primary Topic
Frailty in Older Adults
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Association of an inflammaging score based on IL-6, IL-10 and CXCL9, and frailty with long-term mortality in hospitalized older adults

Antonio Cherubini, Anna Rita Bonfigli, Luca Soraci, Sonia Fantone et al.
Immunity & Ageing
Frailty in Older Adults
article

Association of an inflammaging score based on IL-6, IL-10 and CXCL9, and frailty with long-term mortality in hospitalized older adults

Antonio Cherubini, Anna Rita Bonfigli, Luca Soraci, Sonia Fantone, Federica Lenci, Maurizio Cardelli, Mirko Di Rosa, Fabrizia Lattanzio, Marco Malavolta, Antonio Domenico Procopio, Chiara Giordani, Rina Recchioni, Monia Cecati, Elena Tortato, Francesco Piacenza, Jacopo Sabbatinelli, Leonardo Biscetti, Rosanna Maniscalco, Riccardo Sarzani, Matilde Sbriscia, Robertina Giacconi, Roberto Antonicelli, Massimiliano Fedecostante, Olivieri Fabiola, Carlo Fortunato, Angelica Giuliani, Davide Gentilini, Maria Conte, Gretta Veronica Badillo Pazmay, Tiziana Casoli, Giulia Matacchione, Claudio Franceschi, Andrea Corsonello, Luciano Calzari, Silvia Di Valerio, Emanuele Francini, Francesca Marchegiani, Maurizio Burattini, Yuri Rosati, Sara Caccese
article en

Abstract

Aging is accompanied by chronic low-grade inflammation ("inflammaging"), which contributes to increased morbidity and mortality in older adults. This study evaluated the prognostic value of circulating inflammatory biomarkers, i.e. interleukin-6 (IL-6), interleukin-10 (IL-10), and CXCL9, and their integration with frailty for long-term risk stratification. We analyzed 1,009 patients (median age, 84 years) hospitalized in acute care wards of three Italian geriatric hospitals as part of the ReportAGE cohort. Frailty was assessed using a deficit accumulation–based Frailty Index (FI), and serum cytokines were measured by immunoassay. Cytokine-specific risk categories were combined into a composite I3 score (range, 3–9). Cox proportional hazards models adjusted for age, sex, comorbidity burden, polypharmacy, and laboratory variables were used to assess associations with 10-year mortality. In a subset of 237 patients, DNA methylation–based estimates of cytokine levels were also analyzed. Higher I3 scores were independently associated with increased mortality (hazard ratio [HR] 2.42, 95% CI 1.74–3.37 for high vs. low scores), with CXCL9 as the strongest individual predictor (HR 1.69, 95% CI 1.30–2.19). The I3 score improved risk prediction beyond FI alone, and their combination identified four distinct risk groups, with the highest mortality observed among patients with both elevated FI and I3 scores. The integrated model (Clinical variables + FI + I3) achieved the greatest discrimination during the first seven years of follow-up. Serum IL-6 and CXCL9 correlated with their DNA methylation–based estimates, supporting an epigenetic contribution to chronic inflammation. The I3 score complements frailty assessment and enhances long-term mortality prediction in hospitalized older adults.

Immunity & AgeingVol. 22(1)
Marche Polytechnic University (IT), University of Pavia (IT), European Society of Hypertension (IT), IRCCS Istituto Auxologico Italiano (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Istituto Nazionale di Riposo e Cura per Anziani (IT), University of Calabria (IT), N. I. Lobachevsky State University of Nizhny Novgorod (RU), University of Bologna (IT)
Openalex Percentile: Top 49%
Frailty in Older Adults
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.